The long term goal of our research is to define the mechanisms by which the proximal tubule of the mammalian kidney transports sodium, bicarbonate, chloride and water and to characterize the manner by which they are physiologically regulated. To achieve this goal multiple techniques (free-flow micropuncture, in situ microperfusion, in vitro microperfusion, isolated membrane vesicles) are used and the data obtained by these various means are evaluated for internal consistency and integrated into a physiologically meaningful framework. Specific aims are: 1) To further characterize the nature of the sodium-dependent and sodium-independent components of acidification. 2) To examine the role of adaptive changes in Na/H antiporter activity in modulating the rate of acidification. 3) To examine the role of sodium-dependent and sodium-independent mechanisms in the regulation of cell pH. 4) To determine the response of cell pH to changes in luminal and peritubular bicarbonate, Pco2 and pH. 5) To examine the role of cell pH in the regulation of the rate of acidification in response to changes in acid-base and potassium balance, and the administration of various agents such as glucocorticoids or parathormone. 6) To further characterize the luminal and basolateral mechanisms for transcellular Na and Cl transport. 7) To obtain more precise estimates of the transepithelial driving forces for water movement in vivo.